AB0377 DIFFERENCES OF EFFICACY OF TNF-α INHIBITORS AND THEIR IMMUNOGENICITY IN RHEUMATOID ARTHRITIS AND INFLAMMATORY BOWEL DISEASES
Authors: T. Nuriakhmetova, D. Abdulganieva, A. Vasiliev, N. Cheremina, J. Shevnina
Journal: Annals of the Rheumatic Diseases (2022)

Background The immunogenicity of TNF-α inhibitors (TNFi) and its effect on their efficacy can depend on the underlying disease. To date, no studies were performed to directly compare this relation between different groups of immune-mediated diseases. Objectives To compare the effect of immunogenicity of TNFi on their efficacy in rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD) (Crohn’s disease (CD) and ulcerative colitis (UC)). Methods 20 patients with RA and 53 patients with IBD (38 (30.9%) with CD and 15 (12.2%) with UC) were observed for 17 [10; 27] months. 26 (35.6%) of them received infliximab (INX) infusions, 23 (31.5%) – adalimumab (ADM) and 24 (32.9%) – certolizumab pegol (CZP). The following criteria were used for the evaluation of the response to TNFi: EULAR criteria for RA, decrease of CDAI for CD and Mayo Score for UC. Trough level of TNFi and the level of anti-drug antibodies (ADAb) were measured in the serum samples drawn directly before the planned drug administration. The threshold for low trough level was determined as follows: 1 μg/mL for INX 1 in RA group and 5 μg/mL for INX 2 in IBD group, 5 µg/ml for ADM 3 , and 20 µg/l for CZP 4 . Results 17 (85%) patients with RA and 35 (66%) patients with IBD responded well to the treatment. Loss of response to the treatment developed in 3 (15%) cases of RA and 18 (34%) cases of IBD (p&gt;0.05). The median trough level of INX was 0.22 [0.17; 6.19] µg/ml in RA and 1.56 [0.79; 3.87] µg/ml in IBD. The median trough level of ADM was 5.45 [1.05; 12.07] μg/mL in RA and 11.17 [3.19; 13.01] μg/mL in IBD. The tendency toward lower median trough level of CZP in IBD was observed (28.17 [20.69; 42.95] μg/mL in IBD vs 16.92 [8.31; 30.96] μg/mL in RA (p=0.09)). Low trough level of TNFi was found in 11 (55%) patients with RA and 27 (50.9%) patients with IBD. It did not differ significantly either between the diseases or between the TNFi (p&gt;0.05). Loss of response was associated with low trough level of TNFi in all 3 cases of RA and in IBD – in 9 (50%) cases (p&gt;0.05). Positive ADAb were detected in 6 (30%) patients with RA and 8 (15.1%) patients with IBD. The rate of positive ADAb was comparable between different TNFi and immune-mediated diseases (p&gt;0.05). A tendency toward lower prevalence of ADAb to ADM in CD than in RA was observed (0% vs 40%, OR 0.6, 95%CI 0.362 to 0.995, p=0.08). Association of loss of response to the treatment with ADAb was observed in 2 (66.7%) patients with RA and 2 (11.1%) patients with IBD. Inefficacy of TNFi due to immunogenicity was 6 times more frequent in RA than in IBD (OR 6.0, 95%CI 1.296 to 27.769, p=0.08). Conclusion All RA patients not responding to TNFi treatment had either low trough level of the drug or ADAb as opposed to IBD patients with inefficacy, half of which did not have ADAb or low trough level. References [1]Takeuchi T, Miyasaka N, Tatsuki Y, Yano T, Yoshinari T, Abe T, et al. Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis. Ann Rheum Dis (2011) 70:1208–15. 10.1136/ard.2011.153023 [2]Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology 2017;153:827-34. 10.1053/j.gastro.2017.07.032 [3]Bartelds GM, Krieckaert CL, Nurmohamed MT, van Schouwenburg PA, Lems WF, Twisk JW, Dijkmans BA, Aarden L, Wolbink GJ. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305:1460–1468. doi: 10.1001/jama.2011.406. [4]Gehin, J.E., Goll, G.L., Warren, D.J. et al. Associations between certolizumab pegol serum levels, anti-drug antibodies and treatment response in patients with inflammatory joint diseases: data from the NOR-DMARD study. Arthritis Res Ther 21, 256 (2019). https://doi.org/10.1186/s13075-019-2009-5 Disclosure of Interests Tatiana Nuriakhmetova Grant/research support from: grant for the purchase of laboratory kits from Novartis ltd, Diana Abdulganieva: None declared, Artem Vasiliev: None declared, Natalya Cheremina: None declared, Jana Shevnina: None declared